Effects of Small Molecular Antioxidants on Cerulein-induced Acute Pancreatitis in Rat

It has been suggested that oxygen free radicals are involved in the initiation process of acute pancreatitis, although its pathogenesis is not clear. This study evaluates the roles of oxygen radicals and the effects of small molecular antioxidants (rebamipide, N-acetyl-cysteine, allopurinol, ${\beta}-carotene)$ on the development of cerulein-induced acute pancreatitis. Acute edematous pancreatitis was induced by the intravenous infusion of cerulein at supramaximal dose of 10 ${\mu}g/kg/hour$ for 3.5 hours. The effects of antioxidants, rebamipide (100 mg/kg, i.p.), N-acetyl-cysteine (200 mg/kg, i.v.), allopurinol (20 mg/kg/hour), ${\beta}-carotene$ (50 mg/kg, i.p.), were examined. Cerulein administration resulted in a significant increase in serum amylase activity and pancreatic malondialdehyde (MDA), but not glutathione peroxidase (GSHpx). The glutathione (GSH) content in pancreatic tissue decreased dramatically. Pretreatment of N-acetyl-cysteine significantly decreased the cerulein-induced hyperamylasemia and maintained GSH content in pancreas, but MDA was slightly decreased. In addition, N-acetyl-cysteine ameliorated histological damage. Allopurinol and ${\beta}-carotene$ attenuated cerulein-induced hyperamylasemia, but histologically there was no difference from control. These results indicate that oxygen free radicals play an important role in the initiation of experimental acute pancreatitis. N-acetyl-cysteine is an effective antioxidant that ameliorates the cerulein-induced acute pancreatitis, and the possible therapeutic application of antioxidants against acute pancreatitis needs a further evaluation.